Combination therapy with intranasal NGF and electroacupuncture enhanced cell proliferation and survival in rats after stroke

Abstract

Objective: This work was designed to investigate the effects of the combination therapy with intranasal (IN) administration of nerve growth factor (NGF) and electroacupuncture (EA) on neural progenitors and neurological functional recovery in adult rats after focal ischemia.Methods: Rats subjected to 2 hours of middle cerebral artery occlusion (MCAO) were randomly assigned to four groups: Group 1, IN administration of phosphate-buffered saline (PBS) for control; Group 2, IN administration of NGF alone; Group 3, EA with IN administration of PBS; Group 4, IN administration of NGF with EA. Treatments were initiated at 2 hours after MCAO and continued for three consecutive days. All animals received daily injections of 5-bromodeoxyuridine (BrdU) intraperitoneally for 7 days starting at 24 hours after reperfusion and were killed at 2 hours or 21 days after the last BrdU injection. Neurological function and infarct volume were evaluated. Immunohistochemistry for BrdU was performed to identify newborn cells in the ipsilateral subventricular zone and striatum.Results: The combination treatment led to significant improvement in neurological function and reduction in infarct volume. Cell proliferation and survival of progenitors were enhanced in rats treated with the combination treatment.Conclusion: These results suggest that IN administration of NGF and EA may have a synergistic effect in preventing ischemic injury and enhancing functional recovery after focal cerebral ischemia, which may be attributed to enhanced cell proliferation and survival.